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来自不同地区的疫苗候选基因中低等位基因多样性为肝片吸虫免疫带来了希望。

Low allelic diversity in vaccine candidates genes from different locations sustain hope for Fasciola hepatica immunization.

作者信息

Dominguez Maria Fernanda, González-Miguel Javier, Carmona Carlos, Dalton John P, Cwiklinski Krystyna, Tort José, Siles-Lucas Mar

机构信息

Departamento de Genética, Facultad de Medicina, Universidad de la Republica, UDELAR, Montevideo, Uruguay.

Parasitology Unit, IRNASA-CSIC, Salamanca, Spain.

出版信息

Vet Parasitol. 2018 Jul 15;258:46-52. doi: 10.1016/j.vetpar.2018.06.011. Epub 2018 Jun 11.

Abstract

Fasciola hepatica is a trematode parasite that causes fasciolosis in animals and humans. Fasciolosis is usually treated with triclabendazole, although drug-resistant parasites have been described in several geographical locations. An alternative to drug treatment would be the use of a vaccine, although vaccination studies that have been performed mainly in ruminants over the last 30 years, show high variability in the achieved protection and are not yet ready for commercialisation. Since F. hepatica exhibits a high degree of genomic polymorphism, variation in vaccine efficacy could be attributed, at least partially, to phenotypic differences in vaccine candidate sequences amongst parasites used in the challenge infections. To begin to address this issue, a collection of F. hepatica isolates from geographically dispersed regions, as well as parasites obtained from vaccination trials performed against a field isolate from Uruguay and the experimentally maintained South Gloucester isolate (Ridgeway Research, UK), were compiled to establish a F. hepatica Biobank. These collected isolates were used for the genetic analysis of several vaccine candidates that are important in host-parasite interactions and are the focus of the H2020 PARAGONE vaccine project (https://www.paragoneh2020.eu/), namely FhCL1, FhCL2, FhPrx, FhLAP and FhHDM. Our results show that F. hepatica exhibits a high level of conservation in the sequences encoding each of these proteins. The consequential low variability in these vaccine candidates amongst parasites from different geographical regions reinforces the idea that they would be suitable immunogens against liver fluke isolates worldwide.

摘要

肝片吸虫是一种吸虫寄生虫,可导致动物和人类患肝片吸虫病。肝片吸虫病通常用三氯苯达唑治疗,不过在几个地理位置已发现有耐药性寄生虫。药物治疗的替代方法是使用疫苗,尽管过去30年主要在反刍动物中进行的疫苗接种研究显示,所获得的保护效果差异很大,且尚未准备好商业化。由于肝片吸虫表现出高度的基因组多态性,疫苗效力的差异至少部分可归因于攻击感染中所使用的寄生虫之间候选疫苗序列的表型差异。为了开始解决这个问题,收集了来自地理上分散地区的肝片吸虫分离株,以及从针对乌拉圭的一株野外分离株和实验保存的英国南格洛斯特分离株(Ridgeway Research公司)进行的疫苗接种试验中获得的寄生虫,以建立一个肝片吸虫生物样本库。这些收集到的分离株用于对几种在宿主-寄生虫相互作用中很重要且是H2020 PARAGONE疫苗项目(https://www.paragoneh2020.eu/)重点的候选疫苗进行遗传分析,即FhCL1、FhCL2、FhPrx、FhLAP和FhHDM。我们的结果表明,肝片吸虫在编码这些蛋白质的每一种的序列中表现出高度的保守性。这些候选疫苗在来自不同地理区域的寄生虫之间的低变异性进一步证明,它们将是针对全球肝片吸虫分离株的合适免疫原。

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